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Abstract Background The ongoing global crisis of Higher Education (HE) institutions during the post-COVID-19 pandemic period has increased the likelihood of enduring psychological stressors for staff. This study aimed to identify factors associated with job insecurity, burnout, psychological distress and coping amongst staff working at HE institutions globally. Methods An anonymous cross-sectional study was conducted in 2023 with staff at HE institutions across 16 countries. Job insecurity was measured using the Job Insecurity Scale (JIS), burnout using the Perceived Burnout measure question, psychological distress using the Kessler Psychological Distress Scale (K10), and coping using the Brief Resilient Coping Scale. Multivariable logistic regression with a stepwise variable selection method was used to identify associations. Results A total of 2,353 staff participated; the mean age (± SD) was 43(± 10) years and 61% were females. Most staff (85%) did not feel job insecurity, one-third (29%) perceived burnout in their jobs, more than two-thirds (73%) experienced moderate to very high levels of psychological distress, and more than half (58%) exhibited medium to high resilient coping. Perceived job insecurity was associated with staff working part-time [Adjusted Odds Ratio 1.53 (95% Confidence Intervals 1.15–2.02)], having an academic appointment [2.45 (1.78–3.27)], having multiple co-morbidities [1.86 (1.41–2.48)], perceived burnout [1.99 (1.54–2.56)] and moderate to very high level of psychological distress [1.68 (1.18–2.39)]. Perceived burnout was associated with being female [1.35 (1.12–1.63)], having multiple co-morbidities [1.53 (1.20–1.97)], perceived job insecurity [1.99 (1.55–2.57)], and moderate to very high levels of psychological distress [3.23 (2.42–4.30)]. Staff with multiple co-morbidities [1.46 (1.11–1.92)], mental health issues [2.73 (1.79–4.15)], perceived job insecurity [1.61 (1.13–2.30)], and perceived burnout [3.22 (2.41–4.31)] were associated with moderate to very high levels of psychological distress. Staff who perceived their mental health as good to excellent [3.36 (2.69–4.19)] were more likely to have medium to high resilient coping. Conclusions Factors identified in this study should be considered in reviewing and updating current support strategies for staff at HE institutions across all countries to reduce stress and burnout and improve wellbeing.

Objective: Major depressive disorder (MDD) is an important psychiatric illness worldwide. We developed the Chen Depression Scale (CDS) based on the criteria of the Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition. In this study, we intended to evaluate the psychometric properties of the CDS. Methods: The sample consisted of 135 adult participants aged between 20 and 64 years, including 85 individuals with MDD recruited at a teaching hospital, and 50 community-based non-MDD controls. Depressive symptoms were assessed using CDS and the Chinese version of the Patient Health Questionnaire 9 (C-PHQ-9). We investigated the psychometric properties of CDS, including test–retest reliability, internal consistency reliability, sensitivity and specificity, convergent validity, discriminant validity, and construct validity. Results: The result showed that the CDS had excellent internal reliability (Cronbach’s α = 0.957) and test–retest reliability (intraclass correlation coefficient = 0.843). Construct validity was examined with confirmatory factor analyses to verify the factor structure of the CDS and convergent validity with C-PHQ-9 with a statistically high correlation with Pearson’s r with p < 0.001. When evaluating the impairment criterion for identifying individuals with MDD, those who reported impairment in MDD symptoms and scored a CDS of 17 or above exhibited a sensitivity of 0.86 and a specificity of 0.96 for CDS. Conclusion: The CDS has good psychometric properties, including excellent reliability and sensitivity and diagnostic properties at cutoff point 17. It serves effectively as a screening tool for both clinical diagnosis and academic study of depression.

Levels of progesterone, an endogenous female hormone, increase after ovulation; progesterone is crucial in the luteal phase to maintain successful pregnancy and prevent early miscarriage. Both endogenous and exogenous progesterone are recycled between the liver and gut; thus, the gut microbiota regulate host progesterone levels by inhibiting enterohepatic progesterone circulation. Our data indicated Clostridium innocuum as a major species involved in gut progesterone metabolism in women with infertility. C. innocuum converts progesterone into the neurosteroid epipregnanolone (with negligible progestogenic activity). We purified and characterized the corresponding enzyme, namely NADPH-dependent 5β-dihydroprogesterone reductase, which is highly oxygen sensitive and whose corresponding genes are prevalent in C. innocuum. Moreover, C. innocuum–administered female C57BL/6 mice (aged 7 weeks) exhibited decreased plasma progesterone levels (~35%). Clostridium-specific antibiotics (metronidazole) restored low plasma progesterone levels in these mice. Furthermore, prolonged C. innocuum administration (12 weeks) arrested ovarian follicular development in female mice. Cytological and histological analyses indicated that C. innocuum may cause luteal phase insufficiency and affect menstrual regularity. Our findings suggest C. innocuum as a causal factor of progesterone resistance in women taking progesterone.

Background/Objectives: The complex association between attention-deficit/hyperactivity disorder (ADHD) and methylphenidate (MPH) with precocious puberty (PP) is still unclear. This study aims to investigate the association between ADHD, MPH, and PP. Methods: This is a nationwide cohort study including a total of 3,342,077 individuals, 186,681 with ADHD and 3,155,396 without. First, we compared the risk of PP between ADHD cases and non-ADHD cases. Second, we compared the risk of PP between MPH users and non-MPH users in patients with ADHD. Results: Patients with ADHD were at a greater risk of PP (adjusted hazard ratio [aHR], 2.01 [95% CI, 1.91–2.11]). In our moderation analyses, the female gender was a positive additive effect modifier of the association between ADHD and PP, whereas tics and intellectual disability were negative effect modifiers. In patients with ADHD, MPH users had a significantly lower risk of PP (aHR, 0.63 [95% CI 0.57–0.70]), and females had a negative effect modification on the association between MPH and PP. Conclusions: Our study found that children with ADHD were at a greater risk of PP. Girls with ADHD were a group particularly vulnerable to PP. Comorbid tics or intellectual disability was associated with a lower risk of PP. Among patients with ADHD, MPH was protective against PP, especially in girls. However, these preliminary results need further validation due to the nature of them being from an electronic database study. Unmeasured confounding factors might affect the association between MPH and PP.

Objectives: The present study analyzed the reciprocal relationships between four common pediatric ophthalmic diseases (i.e., hyperopia, myopia, astigmatism, and strabismus) and attention‐deficit/hyperactivity disorder (ADHD) in children. Methods: This study enrolled 86,028 children with ADHD and 1,798,673 children without ADHD in the Taiwan Maternal and Child Health Database who were born at any time from 2004 to 2017. Cox proportional hazards regression models were used to estimate the bidirectional relationships of the four ophthalmic diseases with ADHD in children after adjusting for age, sex, and gestational age at birth. Survival curves for time-to-event variables were estimated using the Kaplan-Meier method, and the log-rank test was used to compare the curves. Results: The results indicated that ADHD significantly predicted the occurrence of hyperopia, myopia, astigmatism, and strabismus. Furthermore, hyperopia, myopia, astigmatism, and strabismus significantly predicted the occurrence of ADHD. The time between enrollment and ADHD diagnosis was shorter for patients with ophthalmic diseases than for the control group, and the time between enrollment and ophthalmic disease diagnosis was also shorter for ADHD patients than for the control group. Sex differences were found in the associations between ADHD and ophthalmic diseases. Conclusion: Clinicians should monitor children with ADHD for hyperopia, myopia, astigmatism, and strabismus to ensure appropriate treatment, and vice versa.

Abstract The present study aimed to investigate the factors associated with the level of rumination about the war among people living in Poland and Ukraine. This cross‐sectional study recruited internet users from advertisements on social media. Levels of rumination, Depression, Anxiety and Stress Scale (DASS), Impact of Event Scale‐Revised (IES‐R), time spent on news of the war, and related demographic variables were collected. The reliability and construct validity of rumination were estimated. Potential factors associated with the level of rumination were identified using univariate linear regression analysis, and further entered into a stepwise multivariate linear regression model to identify independent factors. Due to the non‐normality of distribution, multivariate linear regression with 5000 bootstrap samples was used to verify the results. A total of 1438 participants were included in the analysis, of whom 1053 lived in Poland and 385 lived in Ukraine. The questionnaires on rumination were verified to have satisfactory reliability and validity. After analysis with stepwise and bootstrap regression, older age, female gender, higher DASS and IES‐R scores, and longer time spent on news of the war were significantly associated with higher levels of rumination for both people living in Poland and Ukraine. Lower self‐rated health status, history of chronic medical illness and coronavirus disease 2019 infection were also positively associated with rumination for people living in Poland. We identified several factors associated with the level of rumination about the Russo‐Ukrainian War. Further investigations are warranted to understand how rumination affects individuals’ lives during crises such as war.

Objectives The majority of female immigrants who are married in Taiwan often face a variety of stresses, which may lead to physical or mental illness. Yet few studies have validated the impact of length of residency on physical and mental health using large-scale data. This study combined five nationwide databases and explored the impact of length of residency in Taiwan on the physical and mental health of female marriage immigrants.Design This is a retrospective cohort study.Setting Taiwan.Participants A total of 168 202 female immigrants, who were registered in the national health insurance database from 2001 to 2017, were enrolled for analysis.Measure The length of residency was taken as the period from their first appearance in the national health insurance database to the end of 2017. Hypertension and diabetes were chosen as indices of physical health and depression as an index of mental health. Diagnosis standards were based on the International Classification of Disease, ninth or 10th Revision.Results The physical and mental health of the immigrants deteriorated with increasing time of residence in Taiwan. Immigrants who had resided in Taiwan for 5–10 years or ≥10 years, respectively, had a 5.8-fold (95% CI: 3.46 to 9.74) or 6.29-fold (95% CI: 4.61 to 8.59) higher adjusted risk of developing hypertension; a 3.97-fold (95% CI: 2.54 to 6.21) or 9.18-fold (95% CI: 5.48 to 15.38) higher adjusted risk of developing diabetes; and a 5.01-fold (95% CI: 3.14 to 8.01) or 12.19-fold (95% CI: 8.65 to 17.18) higher adjusted risk of developing depression than their counterparts who had lived in Taiwan for ≤5 years.Conclusion These findings suggest the time elapsed since migration can be a factor in the deterioration of both physical and mental health among female marriage immigrants in Taiwan.

ABSTRACTAbnormally high circulating androgen levels have been considered a causative factor for benign prostatic hypertrophy and prostate cancer in men. Recent animal studies on gut microbiome suggested that gut bacteria are involved in sex steroid metabolism; however, the underlying mechanisms and bacterial taxa remain elusive. Denitrifying betaproteobacteria Thauera spp. are metabolically versatile and often distributed in the animal gut. Thauera sp. strain GDN1 is an unusual betaproteobacterium capable of catabolizing androgen under both aerobic and anaerobic conditions. We administered C57BL/6 mice (aged 7 weeks) with strain GDN1 through oral gavage. The strain GDN1 administration caused a minor increase in the relative abundance of Thauera (≤0.1%); however, it has profound effects on the host physiology and gut bacterial community. The results of our ELISA assay and metabolite profile analysis indicated an approximately 50% reduction in serum androgen levels in the strain GDN1-administered male mice. Moreover, androgenic ring-cleaved metabolites were detected in the fecal extracts of the strain GDN1-administered mice. Furthermore, our RT – qPCR results revealed the expression of the androgen catabolism genes in the gut of the strain GDN1-administered mice. We found that the administered strain GDN1 regulated mouse serum androgen levels, possibly because it blocked androgen recycling through enterohepatic circulation. This study discovered that sex steroids serve as a carbon source of gut bacteria; moreover, host circulating androgen levels may be regulated by androgen-catabolizing gut bacteria. Our data thus indicate the possible applicability of androgen-catabolic gut bacteria as potent probiotics in alternative therapy of hyperandrogenism.

Background: The 2022 War in Ukraine has significantly affected the psychological well-being and daily lives of people in many countries. Objective: Two aims of this transnational study were (1) to compare psychological distress and coping strategies among people living in Ukraine, Poland, and Taiwan, (2) to examine whether the associations between various coping strategies (ie. problem-focused coping, emotion-focused coping, and avoidance) and psychological distress (ie. depression, anxiety, stress, posttraumatic stress disorder symptoms, and hopelessness about the ongoing war) differed among people of various countries during the initial stage of the 2022 War in Ukraine. Method: In total, 1,598 participants (362 from Ukraine, 1,051 from Poland, and 185 from Taiwan) were recruited using an online advertisement to complete online survey questionnaires, including the Brief Coping Orientation to Problems Experienced inventory; the 21-item Depression, Anxiety and Stress Scale; the Impact of Event Scale-Revised; and a questionnaire devised to assess the level of hopelessness about the ongoing war. Results: Psychological distress and adoption of coping strategies differed across people of various countries. Among Taiwanese and Polish respondents, avoidant coping strategies were most strongly associated with all categories of psychological distress compared with problem- and emotion-focused coping strategies. However, the associations of various coping strategies with psychological distress differed to a less extent among Ukrainian respondents. In addition, problem- and emotion-focused coping strategies had comparable associations with psychological distress among the people of Ukraine, Poland, and Taiwan. Conclusions: The 2022 War in Ukraine has affected the psychological well-being of people, especially the Ukrainians. Because of the strong association between the adoption of avoidance coping strategies and psychological distress, despite a less extent among Ukrainian respondents, adaptive coping strategies such as (problem- and emotion-focused) are suggested to help people during times of war.

Abstract Ukraine has been embroiled in an increasing war since February 2022. In addition to Ukrainians, the Russo-Ukraine war has affected Poles due to the refugee crisis and the Taiwanese, who are facing a potential crisis with China. We examined the mental health status and associated factors in Ukraine, Poland, and Taiwan. The data will be used for future reference as the war is still ongoing. From March 8 to April 26, 2022, we conducted an online survey using snowball sampling techniques in Ukraine, Poland, and Taiwan. Depression, anxiety, and stress were measured using the Depression, Anxiety, and Stress (DASS)-21 item scale; post-traumatic stress symptoms by the Impact of Event Scale-Revised (IES-R) and coping strategies by the Coping Orientation to Problems Experienced Inventory (Brief-COPE). We used multivariate linear regression to identify factors significantly associated with DASS-21 and IES-R scores. There were 1626 participants (Poland: 1053; Ukraine: 385; Taiwan: 188) in this study. Ukrainian participants reported significantly higher DASS-21 (p

This study examined the associations of an attention-deficit/hyperactivity disorder (ADHD) diagnosis, impulsivity, and perceived social support with Internet altruistic behaviors (IABs) in adolescents and the associations of IABs with depression, suicidality, and nonsuicidal self-injury in this group. In total, 176 adolescents aged between 11 and 18 years with ADHD and 173 adolescents without ADHD (matched with the ADHD group by sex and age) participated in this study. The adolescents rated their IABs on the Internet altruistic behavior scale, impulsivity on the Barratt impulsiveness scale version 11, and perceived family and peer support on the family and social relationship domains of the Taiwanese quality of life questionnaire for adolescents. The associations of ADHD, impulsivity, and social support with IABs and the associations of IABs with depression, suicidality, and nonsuicidal self-injury were examined through multivariable linear regression analysis. The present study found that more time spent on the Internet (p < 0.001), greater perceived peer support (p < 0.001), greater impulsiveness characterized by a lack of self-control and perseverance (p < 0.001), poorer ability to plan and look ahead (p < 0.001), and an ADHD diagnosis (p = 0.003) were significantly associated with a higher level of IABs. IABs were not significantly associated with severe depression, suicidality, or nonsuicidal self-injury (all p > 0.05). The results of this study indicated that multiple individual and social factors were associated with IABs in adolescents. IABs were not significantly associated with severe depression, suicidality, or nonsuicidal self-injury in adolescents.

Objectives: Caregiver beliefs about the causes of attention-deficit/hyperactivity disorder (ADHD) may influence caregiver intentions to let children with ADHD receive treatment. In this survey study, we intended to determine the proportion of caregivers who attribute the overemphasis of the education system on child academic performance as the etiology of their children's ADHD and the factors related to this attribution. Methods: In total, 213 caregivers of children with ADHD participated in this study and were asked whether they regarded the overemphasis of the education system on child academic performance as the etiology of their children's ADHD. Affiliate stigma was assessed using the Affiliate Stigma Scale. Each caregiver rated their child's ADHD and oppositional defiant disorder symptoms using the short Chinese version of the Swanson, Nolan, and Pelham, Version IV Scale. The depression and anxiety of the caregivers were assessed using the Beck Depression Inventory and Beck Anxiety Inventory, respectively. Results: The results were found that 58 (27.2%) caregivers regarded the overemphasis of the education system on child academic performance to be the etiology of their children's ADHD. Affiliate stigma of caregivers was significantly associated with caregiver attribution (p < 0.05). Caregiver depression (p < 0.01) and anxiety (p < 0.01) were significantly associated with caregiver attribution of the etiology of ADHD in bivariate logistic regression analysis models; the associations became nonsignificant after the effect of affiliate stigma being considered. Conclusion: Health professionals should consider caregiver-attributed etiologies when they are developing intervention programs for enhancing the mental health of caregivers and their children with ADHD.

Background: Theta burst stimulation (TBS), a patterned repetitive transcranial magnetic stimulation (rTMS) protocol with shorter simulation duration and lower stimulus intensity, could be a better protocol for individuals with autism spectrum disorder (ASD). Our study aimed to explore the impacts of intermittent TBS (iTBS) over the bilateral posterior superior temporal sulcus (pSTS) on intellectually able adults with ASD. Methods: In this randomized, single-blinded, sham-controlled crossover trial, 13 adults with ASD completed iTBS for 5 consecutive days over the bilateral pSTS and inion (as a sham control) in a 16-weeks interval and in a randomly assigned order. The neuropsychological function was measured with the Wisconsin Card Sorting Test (WCST) for cognitive flexibility while the clinical outcomes were measured with both self-rate and parents-rate Autism Spectrum Quotient (AQ) before and after 5-day iTBS interventions. Results: The results revealed significantly immediate effects of multi-session iTBS over the bilateral pSTS on parent-rate autistic symptoms in adults with ASD. The post-hoc analysis revealed the impacts of multi-session iTBS on cognitive flexibility were affected by baseline social-communicative impairment and baseline cognitive performance. Besides, the impacts of multi-session iTBS on clinical symptoms was affected by the concurrent psychotropic medication use and baseline autistic symptoms. Conclusions: Given the caveat of the small sample size and discrepancy of multiple informants, this pilot study suggests the therapeutic potential of 5-day multi-session iTBS over the pSTS in adults with ASD. Individual factors modulating the response to rTMS should be explicitly considered in the future trial.

Summary Steroidal oestrogens (C18) are contaminants receiving increasing attention due to their endocrine‐disrupting activities at sub‐nanomolar concentrations. Although oestrogens can be eliminated through photodegradation, microbial function is critical for removing oestrogens from ecosystems devoid of sunlight exposure including activated sludge, soils and aquatic sediments. Actinobacteria were found to be key oestrogen degraders in manure‐contaminated soils and estuarine sediments. Previously, we used the actinobacterium Rhodococcus sp. strain B50 as a model microorganism to identify two oxygenase genes, aedA and aedB, involved in the activation and subsequent cleavage of the estrogenic A‐ring respectively. However, genes responsible for the downstream degradation of oestrogen A/B‐rings remained completely unknown. In this study, we employed tiered comparative transcriptomics, gene disruption experiments and mass spectrometry‐based metabolite profile analysis to identify oestrogen catabolic genes. We observed the up‐regulation of thiolase‐encoding aedF and aedK in the transcriptome of strain B50 grown with oestrone. Consistently, two downstream oestrogenic metabolites, 5‐oxo‐4‐norestrogenic acid (C17) and 2,3,4‐trinorestrogenic acid (C15), were accumulated in aedF‐ and aedK‐disrupted strain B50 cultures. Disruption of fadD3 [3aα‐H‐4α(3'‐propanoate)‐7aβ‐methylhexahydro‐1,5‐indanedione (HIP)‐coenzyme A‐ligase gene] in strain B50 resulted in apparent HIP accumulation in oestrone‐fed cultures, indicating the essential role of fadD3 in actinobacterial oestrogen degradation. In addition, we detected a unique meta‐cleavage product, 4,5‐seco‐estrogenic acid (C18), during actinobacterial oestrogen degradation. Differentiating the oestrogenic metabolite profile and degradation genes of actinobacteria and proteobacteria enables the cost‐effective and time‐saving identification of potential oestrogen degraders in various ecosystems through liquid chromatography–mass spectrometry analysis and polymerase chain reaction‐based functional assays.

BackgroundMothers and children in families with one immigrant parent have been reported to be healthier than those in native families; however, the health of the fathers in these families has rarely been discussed in literature. ObjectiveWe aimed to comprehensively compare the health of all the family members between families with one immigrant parent (native fathers, immigrant mothers, and their children) and native families (native fathers, native mothers, and their children). MethodsWe conducted a cohort study by using the Taiwan Maternal and Child Health Database to recruit live-born children and their parents from 2004 to 2016. Overall, we identified 90,670 fathers, 91,270 mothers, and 132,457 children in families with one immigrant parent and 1,666,775 fathers, 1,734,104 mothers, and 2,637,191 children in native families and followed up with them from 2004 to 2017. The outcomes comprised common physical and mental disorders, catastrophic illnesses, mortality, and child adversities and accidents. The covariates comprised the child’s year of birth, parental age, low-income status, and physical or mental disorder status. Logistic regression was performed to compare the risks of the outcomes between families with one immigrant parent and native families. ResultsThe parents in families with one immigrant parent were more likely to be of low-income status and were older than the parents in native families. After adjusting for the covariates, fathers in families with one immigrant parent were found to have higher risks of physical and mental disorders, catastrophic illness, and mortality than fathers in native families. Conversely, mothers in families with one immigrant parent had lower risks of physical and mental disorders, catastrophic illness, and mortality than mothers in native families. Finally, the children in families with one immigrant parent generally had better physical and mental health but higher risks for leukemia, liver diseases, autism spectrum disorder, and road traffic accidents than children in native families. ConclusionsThe health status of the members of families with one immigrant parent was nonhomogeneous, and the poorer general health of fathers in such families suggests health inequalities in families with one immigrant parent.

Abstract Methamphetamine (METH) use, most prevalent in young adults, has been associated with high rates of morbidity and mortality. The relationship between METH use and accelerated biological aging, which can be measured using leukocyte telomere length (LTL), remains unclear. We examined whether young adult METH users have shorter LTL and explored the relationship between characteristics of METH use and LTL by using Mendelian randomization (MR) analysis. We compared the LTL for 187 METH users and 159 healthy individuals aged between 25 and 34 years and examined the relationship of LTL with METH use variables (onset age, duration, and maximum frequency of METH use) by using regression analyses. In addition, 2-stage-least-squares (2SLS) MR was also performed to possibly avoid uncontrolled confounding between characteristics of METH use and LTL. We found METH users had significantly shorter LTL compared to controls. Multivariate regression analysis showed METH use was negatively associated with LTL (β = −0.36, P

ObjectivesThis is the first study to examine health care utilization in terms of medical use and costs in native fathers and children from transnational families.MethodsTaiwan National Health Insurance Research Database was used to compare the annual medical use and inflation-adjusted medical cost for ambulatory care from 2004 to 2017 between native fathers and children from transnational and native families.ResultsNative fathers from transnational families had lower annual medical use (−0.23 visits) but higher total medical costs (New Taiwan dollars, NT$, 966), especially in dialysis and psychiatry, compared with those from native families. Unlike fathers from transnational families, their children were observed to consistently have lower medical use (−1.35 visits) and costs (NT$ −636), compared with those from native families.ConclusionsThere was different medical use and costs in transnational marriage families, possibly as a result of features in transnational marriage families. These findings provide insight for future health care policies to address the different health care utilization by exploring the unmet needs and barriers relating to children and fathers from transnational families.

The gut microbiome is essential for a host to digest food, maintain health, and adapt to environments. Bacterial communities of gut microbiota are influenced by diverse factors including host physiology and the environment. Many non-human primates (NHPs), which are physiologically close to humans, are in danger of extinction. In this study, the community structure of the gut microbiota in three NHPs: siamangs (Symphalangus syndactylus, Ss), Bornean orangutans (Pongo pygmaeus, Pp), and white-handed gibbons (Hylobates lar, Hl)—housed at the largest Zoo in Taiwan were analyzed. Pp and Ss were housed in the Asian tropical rainforest area, while Hl was housed in two separate areas, the Asian tropical rainforest area and the conservation area. Bacterial community diversity of Ss, indicated by the Shannon index, was significantly higher compared with that of Hl and Pp, while the richness (Chao 1) and observed operational taxonomic units (OTUs) were similar across the three species of NHPs. Host species was the dominant factor shaping the gut microbial community structure. Beta-diversity analysis including non-metric multidimensional scaling (NMDS) and unweighted pair group method with arithmetic mean (UPGMA) suggested gut bacterial communities of Hl housed in the conservation area were closely related to each other, while the bacterial communities of Hl in the rainforest area were dispersedly positioned. Further analysis revealed significantly higher abundances of Lactobacillus fermentum, L. murinus, and an unclassified species of Lactobacillus, and a lower abundance of Escherichia-Shigella in Hl from the conservation area relative to the rainforest area. The ratio of Lactobacillus to Escherichia-Shigella was 489.35 and 0.013 in Hl inhabiting the conservation and rainforest areas, respectively. High abundances of Lactobacillus and Bifidobacterium and a high ratio of Lactobacillus to Escherichia-Shigella were also observed in one siamang with notable longevity of 53 years. Data from the study reveal that host species acted as the fundamental driving factor in modulating the community structure of gut microbiota, but that habitats also acted as key determinants within species. The presence and high abundance of probiotics, such as Bifidobacterium and Lactobacillus, provide potential indicators for future diet and habitat optimization for NHPs, especially in zoological settings.

Long-term neurological and neurodevelopmental sequelae are a concerning issue for people with Enterovirus A71 (EV-A71) central nervous system (CNS) infection. Unfortunately, no longitudinal prospective clinical study has systematically investigated the consequences of EV-A71 CNS infection during early life on the later development of other psychiatric disorders. In this naturalistic longitudinal follow-up design, we followed forty-three youth, who got EV-A71 CNS involvement 6–18 years ago and were enrolled in other EV-A71 clinical studies then. Their psychiatric presentation, emotional/behavioral problems, and cognitive issues were examined using a psychiatrist-conducted diagnostic interview, parent- and self-rated questionnaires, and neuropsychological tests, respectively. We compared the prevalence of psychiatric disorders in youth with EV-A71 CNS involvement to a nationally representative cohort. Emotion/behavior and cognition in EV-A71-CNS-infected youth were compared to those in a matched community-based sample of healthy controls and youth with attention-deficit/hyperactivity disorder (ADHD). Compared to a national sample (absolute ADHD prevalence 10.1%), youth with EV-A71 CNS involvement had three times the odds of receiving an ADHD diagnosis (standardized prevalence ratio, 95% CI = 1.8, 4.2; absolute ADHD prevalence 34.9%). No other psychiatric diagnoses were more common in EV-A71-CNS-infected youth. Compared to community-based ADHD youth, EV-A71-CNS-infected youth with psychiatric disorders showed comparable core ADHD symptoms, opposition/defiance, autistic features, and suboptimal sustained attention performance (based on the Conners’ Continuous Performance Test), all of which were more severe than healthy controls. EV-A71-CNS-infected youth without psychiatric disorders showed comparable autistic features to EV-A71-CNS-infected youth with psychiatric disorders and ADHD youth. EV-A71 CNS involvement may cause long-term, adverse psychiatric outcomes that develop into an ADHD diagnosis alongside social/communication/emotion problems and autistic features. We recommend earlier identification and intervention of these problems among these children.

Summary Steroidal oestrogens are often accumulated in urban estuarine sediments worldwide at microgram per gram levels. These aromatic steroids have been classified as endocrine disruptors and group 1 carcinogens. Microbial degradation is a naturally occurring mechanism that mineralizes oestrogens in the biosphere; however, the corresponding genes in oestrogen‐degrading actinobacteria remain unidentified. In this study, we identified a gene cluster encoding several putative oestrogen‐degrading genes (aed; actinobacterial oestrogen degradation) in actinobacterium Rhodococcus sp. strain B50. Among them, the aedA and aedB genes involved in oestrogenic A‐ring cleavage were identified through gene‐disruption experiments. We demonstrated that actinobacterial oestrone 4‐hydroxylase (AedA) is a cytochrome P450‐type monooxygenase. We also detected the accumulation of two extracellular oestrogenic metabolites, including pyridinestrone acid (PEA) and 3aα‐H‐4α(3'‐propanoate)‐7aβ‐methylhexahydro‐1,5‐indanedione (HIP), in the oestrone‐fed strain B50 cultures. Since actinobacterial aedB and proteobacterial edcB shared

ABSTRACT Prochlorococcus is the key primary producer in marine ecosystems, and the high-light-adapted clade II (HLII) is the most abundant ecotype. However, the genomic and ecological basis of Prochlorococcus HLII in the marine environment has remained elusive. Here, we show that the ecologically coherent subclade differentiation of HLII corresponds to genomic and ecological characteristics on the basis of analyses of 31 different strains of HLII, including 12 novel isolates. Different subclades of HLII with different core and accessory genes were identified, and their distribution in the marine environment was explored using the TARA Oceans metagenome database. Three major subclade groups were identified, viz., the surface group (HLII-SG), the transition group (HLII-TG), and the deep group (HLII-DG). These subclade groups showed different temperature ranges and optima for distribution. In regression analyses, temperature and nutrient availability were identified as key factors affecting the distribution of HLII subclades. A 35% increase in the relative abundance of HLII-SG by the end of the 21st century was predicted under the Representative Concentration Pathway 8.5 scenario. Our results show that the ubiquity and distribution of Prochlorococcus HLII in the marine environment are associated with the differentiation of diverse subclades. These findings provide insights into the large-scale shifts in the Prochlorococcus community in response to future climate change. IMPORTANCE Prochlorococcus is the most abundant oxygenic photosynthetic microorganism on Earth, and high-light-adapted clade II (HLII) is the dominant ecotype. However, the factors behind the dominance of HLII in the vast oligotrophic oceans are still unknown. Here, we identified three distinct groups of HLII subclades, viz., the surface group (HLII-SG), the transition group (HLII-TG), and the deep group (HLII-DG). We further demonstrated that the ecologically coherent subclade differentiation of HLII corresponds to genomic and ecological characteristics. Our study suggests that the differentiation of diverse subclades underlies the ubiquity and distribution of Prochlorococcus HLII in the marine environment and provides insights into the shifts in the Prochlorococcus community in response to future climate change.

Purpose: To examine the effects of risperidone, an atypical antipsychotic agent, on gastric cancer.Methods: A triangulation method comprising bench studies, including cell and animal experiments, and a retrospective cohort study, was subsequently performed.Results: The bench study indicated that risperidone exerted more prominent tumor inhibition effects than other atypical antipsychotics on the proliferation of KATO-III cells, a human gastric cancer cell line. Significant and dose-dependent cell viability was observed in Hs27 cells (control cells) in the presence of risperidone compared with in KATO-III cells. Both in vivo and in vitro results indicated that risperidone significantly inhibited the proliferation of KATO-III cells by inducing ROS and apoptosis, and that it suppressed the growth of xenografted KATO-III tumors in nude mice. In addition, the population-based cohort study found that risperidone users had reduced risks of gastric cancer compared with non-users, with lowered adjusted hazard ratios (HRs) for two induction periods (HR = 0.75; 95% confidence interval [CI] 0.68–0.83 for the one-year induction period, and HR = 0.68; 95% CI 0.61–0.75 for the two-year induction period).Conclusion: The findings are consistent with anticancer effects associated with risperidone, but further research and evaluations are warranted.

Abstract Background In this study, we examined the differential associations of various proinflammatory and anti-inflammatory cytokines with depression severity from the development of breast cancer to subsequent chemotherapy treatment. Methods A cross-sectional study was conducted on a sample of 116 women: 29 controls without cancer, 55 patients with breast cancer who were not receiving chemotherapy, and 32 patients with breast cancer who were receiving chemotherapy. Blood samples were assayed to evaluate serum levels of the following cytokines: interferon-γ, interleukin (IL)-12 (p70), IL-1β, IL-2, tumor necrosis factor (TNF)-α, IL-4, IL-5, IL-10, IL-13, IL-6, and IL-17A. Depression severity was assessed using the Patient Health Questionnaire. Results After adjustment for sociodemographics, consistent patterns of the association between cytokine and depression were noted in the different groups. No significant associations were observed in the controls. Inverse associations were observed between cytokines levels and depression severity in patients with breast cancer who were not receiving chemotherapy, whereas positive associations were noted in patients with breast cancer who were receiving chemotherapy. Specific differential relationships between IL-5 levels and depression severity were found between patients with breast cancer who were receiving and not receiving chemotherapy. Conclusions Our study revealed differential relationships between cytokine levels and depression severity with the development of cancer. Immunostimulation and immunosuppression in breast cancer and cancer treatment may account for the differential responses with the development of breast cancer.

Background/Purpose: With globalization, transnational marriages become more and more common in the world. The mental health of the offspring of immigrants is a significant public health issue. The present study aimed to investigate whether children of immigrant mothers demonstrate more emotional and behavioral problems than those of native mothers in Taiwan. Methods: In a sample of 6242 children in grade 3, grade 5, and grade 7 from a national epidemiological study of child mental disorders, 617 (9.9%) children were born by immigrant mothers (Chinese, Vietnam, Indonesia, and other countries) and 5625 children by Taiwanese parents. The children reported on Achenbach Youth Self-report, and their parents reported about them on the Child Behavior Checklist, Parental Bonding Inventory, and Family APGAR for assessing emotional and behavioral problems, mother's parenting style, and perceived family support. Results: Compared with children of native mothers, children of immigrant mothers reported themselves and were reported by their parents to have more externalizing and internalizing problems. However, after considering the effects of sociodemographics, parenting style, and family function, only significant differences in externalizing problems between children with native or immigrant mothers were found. Conclusion: Our findings indicate that right parenting style and family support; may offset emotional and behavioral problems in children of immigrant mothers, and suggest that improving maternal parenting and family function is beneficial to child development, regardless of immigrant or native mothers. Keywords: Immigrant, Offspring, Child behaviors, Parenting, Family function

ObjectiveChildren with attention deficit hyperactivity disorder (ADHD) have more visits to the emergency department (ED) due to injuries than those without ADHD. However, no study has investigated whether children with ADHD have more ED visits or hospitalizations due to infectious diseases (IDs) and whether methylphenidate (MPH) treatment may reduce the risk.MethodThe incidence of ID-related ED visits or hospitalizations was defined as the main outcome. The Cox regression and conditional Poisson regression models were calculated to estimate hazard ratios (HRs) in the population level and relative risks for the self-controlled case series design, respectively.ResultsChildren with ADHD had higher rates of emergency visits (HR = 1.25, 95% CI: 1.23~1.27) and hospitalizations (HR = 1.28, 95% CI: 1.26~1.31) due to IDs than those without ADHD. In the ADHD subgroup, those who received MPH treatment have a reduced risk of emergency visits (HR = 0.10, 95% CI: 0.09~0.10) and hospitalizations (HR = 0.73, 95% CI: 0.71~0.75), compared to those without treatment. The risk of ID-related emergency visits decreased to 0.21 (95% CI: 0.21~0.22); and hospitalizations decreased to 0.71 (95% CI: 0.69~0.73). Within self-controlled analysis, it is demonstrated that compared with non-MPH exposed period, children with ADHD had significantly decreased risks for infection-related emergency visits (RR = 0.73, 95% CI: 0.68~0.78) or hospitalizations (RR = 0.19, 95% CI: 0.17~0.21) during MPH-exposed periods.Conclusions and RelevanceThis is the first study that reported an increased risk of ID-related healthcare utilizations in children with ADHD compared to those without, and that such risks may be significantly reduced in ADHD children that received MPH treatment.

Xenobiotic phthalate esters (PAEs) have been produced on a considerably large scale for only 70 years. The occurrence of endocrine-disrupting di-(2-ethylhexyl) phthalate (DEHP) in environments has raised public concern, and estuarine sediments are major DEHP reservoirs.

Background: The different profiles of e-cigarette users in different age groups have seldom been investigated, particularly in populations facing a high prevalence of cigarette smoking. This study aims to examine the prevalence and correlates of e-cigarette use separately for adolescents and adults in nationally representative samples in Taiwan. Methods: Among 17,837 participants in the 2014 National Survey of Substance Use in Taiwan, 4445 were aged 12 to 17 years and 13,392 were aged 18 to 64 years. Individuals’ lifetime tobacco use was divided into four groups: non-use, exclusive e-cigarette use, exclusive cigarette use, and dual use. Questions on sociodemographic features, use and problematic use of tobacco, alcohol, and other drugs, and psychosocial distress, among others, were administered using a computer-assisted self-interview on tablet computers. Results: Among lifetime users of e-cigarette (2.2% for adults and 0.8% for adolescents), 4.5% for adults and 36.6% for adolescents were exclusive e-cigarette users. From use of exclusive e-cigarettes to use of exclusive cigarettes to dual use, those usage groups were related to an increasing trend of adjusted odds ratios for use of other psychoactive substances, particularly problematic use of alcohol or drugs, and with more depressive symptoms. Two correlates were specific to e-cigarette use: alcohol use had stronger relationships with e-cigarette use among adolescents, and younger adults (18–34) were more likely to try e-cigarettes compared to older adults. Conclusions: These results provide essential information regarding e-cigarette use in the general population, and future prevention strategies should account for its specific correlates in young people.

Abstract Background The aims of this study were to explore the relationship between early reduction in psychotic symptoms and the ultimate response in patients with schizophrenia treated by atypical antipsychotics, and to determine the best time to switch or maitain the regimen. We also explore the possible predictors for the clinical response. Methods One hundred eleven inpatients with acutely exacerbated schizophrenia were randomized to give optimal therapy of olanzapine, risperidone, and paliperidone in one-week run-in period and 12 weeks’ intervention. All participants were assessed using Positive and Negative Syndrome Scale (PANSS). Early Response, defined as reduction of 25% in PANSS score, was examined at weeks 1, 2, 3, 4 and 8, and these ratings were used to predict ultimate response (25% PANSS reduction) at week 12. We hypothesized that early treatment response at Week 1 or 2 could predict Week 12’s treatment outcome. Results The early treatment response at Week 2 had a greater negative prediction value (NPV, 93.6%) than did the response at Week 1 (NPV, 69.7%), Week 3 (NPV, 91.5%), Week 4 (NPV, 90.7%) and Week 8 (NPV, 87.2%). The positive predictive value became more acceptable (65%) until Week 4. There was no any other potential predictors, including types of antipsychotics medication and treatment dosage, were associated with ultimate response in this study. Conclusion The treatment non-response at Week 2 optimally predicted the ultimate (Week 12) non-response, in terms of negative predictive value (NPV). These finding suggests that the revision of treatment strategy should be considered t if patients with schizophrenia was not responsive to them after 2 weeks’ treatment, and for those who are responders at Week 2, another two weeks are needed to further evaluate whether they will be continuously responsive. Trial registration NCT03730857 at ClinicalTrial.gov. Date of registration: 30/Oct/2018.

Background: The coronavirus disease 2019 (COVID-19) pandemic spread rapidly, as did COVID-19-related information on diverse media platforms. Excessive COVID-19-related information caused substantial mental distress among the public. Although most studies focused on the impact of information on individuals during the pandemic, they usually focused on information from internet sources, and few studies compared the impacts between different information sources. We examine the sociodemographic profiles of participants receiving different information sources and the impact of various COVID-19-related information sources on public worry. Methods: A cross-sectional online survey with a total of 2007 participants aged 20 years and above recruited anonymously was conducted during the COVID-19 pandemic. The sociodemographic data, frequencies at which participants received COVID-19-related information, the information sources (e.g., traditional media, interpersonal information exchange, and academic courses), and the levels of past, current, and anticipated worry about COVID-19 were assessed. Results: The most common sources of COVID-19-related information were internet media (80.52%), traditional media (52.62%), family members (24.36%), coworkers (23.57%), friends (21.08%), academic courses (20.18%), and medical staff (19.03%). We found that the COVID-19-related information from traditional media, internet media, and friends was associated with higher current worry (the unstandardized regression coefficient, B, ranged from 0.27 to 0.30), and the information from friends was associated with higher past worry (B was 0.18). In contrast, participants who received information from academic courses had lower past worry and anticipated worry (B ranged from −0.15 to −0.17). Conclusions: Academic courses may play a protective role in public worry during the pandemic. Therefore, academic courses and the information they provide may help facilitate public education and reduce public worry in cases of infectious disease outbreaks.

The present study aimed (1) to identify distinct latent classes of motivation to get vaccinated against coronavirus disease 2019 (COVID-19) and previous seasonal influenza vaccination among people in Taiwan and (2) to examine the roles of sources of information, risk perception, and cognitive appraisals of vaccination against COVID-19 in these classes. We recruited 1047 participants through a Facebook advertisement. The participants’ motivation to get vaccinated against COVID-19, previous seasonal influenza vaccination, sources of information about COVID-19 vaccination, risk perception of COVID-19, and cognitive appraisals of vaccination against COVID-19 were determined. We examined the participants’ motivation for COVID-19 vaccination and previous seasonal influenza vaccination through latent profile analysis. Four latent classes of motivation were identified: participants with high motivation for COVID-19 vaccination and high seasonal influenza vaccination, those with high motivation for COVID-19 vaccination but low seasonal influenza vaccination, those with low motivation for COVID-19 vaccination but high seasonal influenza vaccination, and those with low motivation for COVID-19 vaccination and low seasonal influenza vaccination. Compared with participants in the latent class of high motivation for COVID-19 vaccination and high seasonal influenza vaccination, those in the other three latent classes had lower levels of positive appraisals of COVID-19 vaccination; participants in the latent class of low motivation for COVID-19 vaccination and low seasonal influenza vaccination had lower risk perception of COVID-19 and were also less likely to obtain information about COVID-19 vaccination from the internet, friends, and family members. The various motivations and behaviors for vaccination, sources of information, risk perception, and cognitive appraisals of vaccination against COVID-19 should be considered in intervention programs aiming to increase people’s motivation to get vaccinated against COVID-19.

Changes of diagnostic coverage and criteria for psychiatric disorders in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) published in 2013 cause a need for updating the Kiddie-Schedule for Affective Disorders and Schizophrenia-Epidemiological version (K-SADS-E). This study examined the preliminary psychometric properties, including inter-rater reliability, and convergent and divergent validity of the modified K-SADS-E for DSM-5. Methods: A national survey of a school-based sample of 3242 students in grade 3, 5, and 7 from 44 schools was conducted in Northern, Central, and Southern Taiwan. Psychiatric diagnoses were made by the K-SADS-E interviews. Clinical questionnaires for attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and emotional and behavioral problems were examined using the Chinese version of the Swanson, Nolan, and Pelham IV scale, Social Responsiveness Scale, and Child Behavior Checklist. Results: The K-SADS-E showed satisfactory inter-rater reliability (prevalence adjusted bias adjusted kappa = 0.80–1.00) among eight interviewers. The diagnoses of K-SADS-E demonstrated good convergent and divergent validity with most corresponding clinical questionnaires. Conclusion: Our finding suggests that the K-SADS-E is a reliable and valid instrument for diagnosing child and adolescent psychiatric disorders based on DSM-5. Further study will examine the sensitivity, specificity, and test–retest reliability of the K-SADS-E in clinical and community samples.

Abstract Background Several longitudinal studies have shown the partial symptomatic persistence of attention-deficit hyperactivity disorder (ADHD) in clinic-based samples. However, little is known about the patterns and trajectories of ADHD symptoms in community-based populations. Methods To differentiate developmental trajectories of ADHD symptoms over 1 year, with a four-wave quarterly follow-up in children and adolescents in the community of Taiwan, we conducted this prospective study in 1281 students in grade 3, 5, and 8. All the students in the regular classes rather than special educational classes were eligible and recruited to the study. Inattention, hyperactivity–impulsivity, and opposition-defiance were rated by parent reports on the Chinese version of the Swanson, Nolan, and Pelham Version IV Scale (SNAP-IV). Group-based trajectory modeling and multivariable regression analyses were used to explore the individual, family and social factors associated with differential trajectories. Results Trajectories were classified as Low (29.9–40.6%), Intermediate (52.5–58.5%) and High (6.9–12.5%) based on the symptom severity of ADHD symptoms assessed by the SNAP-IV. The proportion of children in the high ADHD trajectory might approximately reflect the prevalence of ADHD in Taiwan. The following factors differentiated High from Low trajectories: male gender, more externalizing problems, fewer prosocial behaviors, school dysfunction, more home behavioral problems, and less perceived family support. Conclusions Our findings that the concurrent conditions of emotional or externalizing problems, as well as impaired school and home function at baseline, might differentiate the high ADHD symptoms trajectory from others could help developing the specific measures for managing high ADHD symptoms over time in a school setting.

Nonmedical prescription drug use (NMPDU) has become a major public health issue but little is known in Asian populations. This study aimed to investigate the prevalence and correlates of NMPDU in Taiwan. Participants from the 2014 national survey of 17,837 individuals, aged 12 to 64 year, completed anonymously a computer-assisted self-interview. Past-year prescription drug use was divided into medical use only (MUO) and nonmedical use (NMU), defined as using the drug without a prescription, or more frequently, or in larger doses than prescribed. Problematic alcohol use was measured using the Alcohol Use Disorders Identification Test (AUDIT), problematic drug use using the 20-item Drug Abuse Screening Test (DAST), and depressive symptoms using the Center for Epidemiological Study-Depression (CES-D). The prevalence of past-year NMU was 3.02% for analgesics, 0.71% for sedatives/hypnotics, and 3.66% for either drug, with a very small overlap of NMU between analgesics and sedatives/hypnotics (0.07%). When individuals with NMU were compared to those without NMU (Non-NMU) and those with MUO, respectively, some correlates consistently identified, including young adulthood, tobacco smoking, alcohol drinking, and greater AUDIT's scores for analgesics, as well as hard drug use and greater DAST's scores for sedatives/hypnotics. NMU was associated with greater CES-D's scores for both analgesics and sedatives/hypnotics when compared to Non-NMU but not to MUO. Robust correlates of NMPDU could offer implications for development of prevention strategies of NMPDU. Keywords: Nonmedical use, Sedatives/hypnotics, Analgesics, Substance use, Illicit drug

Bacteriophages substantially contribute to bacterial mortality in the ocean and play critical roles in global biogeochemical processes. Alteromonas is a ubiquitous bacterial genus in global tropical and temperate waters, which can cross-protect marine cyanobacteria and thus has important ecological benefits. However, little is known about the biological and ecological features of Alteromonas phages (alterophages). Here, we describe a novel alterophage vB_AmeP-R8W (R8W), which belongs to the Autographiviridae family and infects the deep-clade Alteromonas mediterranea. R8W has an equidistant and icosahedral head (65 ± 1 nm in diameter) and a short tail (12 ± 2 nm in length). The genome size of R8W is 48,825 bp, with a G + C content of 40.55%. R8W possesses three putative auxiliary metabolic genes encoding proteins involved in nucleotide metabolism and DNA binding: thymidylate synthase, nucleoside triphosphate pyrophosphohydrolase, and PhoB. R8W has a rapid lytic cycle with a burst size of 88 plaque-forming units/cell. Notably, R8W has a wide host range, such that it can infect 35 Alteromonas strains; it exhibits a strong specificity for strains isolated from deep waters. R8W has two specific receptor binding proteins and a compatible holin–endolysin system, which contribute to its wide host range. The isolation of R8W will contribute to the understanding of alterophage evolution, as well as the phage–host interactions and ecological importance of alterophages.

Camouflaging is a strategy adopted by neurodivergent individuals to cope in neurotypical social contexts, likely related to perceived stress. Despite increasing research in autistic adults, studies of camouflaging in adolescents remain sparse. The self-reported Camouflaging Autistic Traits Questionnaire has been validated in adults in some Western societies, but not in non-Western populations. We examined the psychometric properties of the self-reported and caregiver-reported Chinese version Camouflaging Autistic Traits Questionnaire in Taiwanese adolescents. We enrolled 100 autistic and 105 non-autistic adolescents (aged 12-18 years) and their caregivers. As an initial development, we found a two-factor structure ("compensation-masking" and "assimilation") via exploratory factor analysis, alongside good internal consistency and test-retest reliability, for both the self-reported and caregiver-reported Chinese version Camouflaging Autistic Traits Questionnaire. Self-reported and caregiver-reported Chinese version Camouflaging Autistic Traits Questionnaire scores were moderately to highly correlated. Autistic adolescents showed higher total Chinese version Camouflaging Autistic Traits Questionnaire and assimilation scores than non-autistic adolescents in both males and females. Female autistic adolescents showed higher assimilation than male autistic adolescents, but there was no significant difference between sex assigned at birth on compensation-masking in either autistic or non-autistic adolescents. Assimilation correlated with higher self-perceived stress for both autistic and non-autistic adolescents. Both self-reported and caregiver-reported Chinese version Camouflaging Autistic Traits Questionnaire were reliable and offered meaningful information to understand social coping of Taiwanese autistic and non-autistic adolescents.

ABSTRACT The 2,3-seco pathway, the pathway for anaerobic cholesterol degradation, has been established in the denitrifying betaproteobacterium Sterolibacterium denitrificans. However, knowledge of how microorganisms respond to cholesterol at the community level is elusive. Here, we applied mesocosm incubation and 16S rRNA sequencing to reveal that, in denitrifying sludge communities, three betaproteobacterial operational taxonomic units (OTUs) with low (94% to 95%) 16S rRNA sequence similarity to Stl. denitrificans are cholesterol degraders and members of the rare biosphere. Metatranscriptomic and metabolite analyses show that these degraders adopt the 2,3-seco pathway to sequentially catalyze the side chain and sterane of cholesterol and that two molybdoenzymes—steroid C25 dehydrogenase and 1-testosterone dehydrogenase/hydratase—are crucial for these bioprocesses, respectively. The metatranscriptome further suggests that these betaproteobacterial degraders display chemotaxis and motility toward cholesterol and that FadL-like transporters may be the key components for substrate uptake. Also, these betaproteobacteria are capable of transporting micronutrients and synthesizing cofactors essential for cellular metabolism and cholesterol degradation; however, the required cobalamin is possibly provided by cobalamin-de novo-synthesizing gamma-, delta-, and betaproteobacteria via the salvage pathway. Overall, our results indicate that the ability to degrade cholesterol in sludge communities is reserved for certain rare biosphere members and that C25 dehydrogenase can serve as a biomarker for sterol degradation in anoxic environments. IMPORTANCE Steroids are ubiquitous and abundant natural compounds that display recalcitrance. Biodegradation via sludge communities in wastewater treatment plants is the primary removal process for steroids. To date, compared to studies for aerobic steroid degradation, the knowledge of anaerobic degradation of steroids has been based on only a few model organisms. Due to the increase of anthropogenic impacts, steroid inputs may affect microbial diversity and functioning in ecosystems. Here, we first investigated microbial functional responses to cholesterol, the most abundant steroid in sludge, at the community level. Our metagenomic and metatranscriptomic analyses revealed that the capacities for cholesterol approach, uptake, and degradation are unique traits of certain low-abundance betaproteobacteria, indicating the importance of the rare biosphere in bioremediation. Apparent expression of genes involved in cofactor de novo synthesis and salvage pathways suggests that these micronutrients play important roles for cholesterol degradation in sludge communities.

Current knowledge on the biochemical mechanisms underlying microbial steroid metabolism in anaerobic ecosystems is extremely limited. Sulfate, nitrate, and iron [Fe (III)] are common electron acceptors for anaerobes in estuarine sediments. Here, we investigated anaerobic testosterone metabolism in anaerobic sediments collected from the estuary of Tamsui River, Taiwan. The anaerobic sediment samples were spiked with testosterone (1 mM) and individual electron acceptors (10 mM), including nitrate, Fe3+, and sulfate. The analysis of androgen metabolites indicated that testosterone biodegradation under denitrifying conditions proceeds through the 2,3-seco pathway, whereas testosterone biodegradation under iron-reducing conditions may proceed through an unidentified alternative pathway. Metagenomic analysis and PCR-based functional assays suggested that Thauera spp. were the major testosterone degraders in estuarine sediment samples incubated with testosterone and nitrate. Thauera sp. strain GDN1, a testosterone-degrading betaproteobacterium, was isolated from the denitrifying sediment sample. This strain tolerates a broad range of salinity (0–30 ppt). Although testosterone biodegradation did not occur under sulfate-reducing conditions, we observed the anaerobic biotransformation of testosterone to estrogens in some testosterone-spiked sediment samples. This is unprecedented since biotransformation of androgens to estrogens is known to occur only under oxic conditions. Our metagenomic analysis suggested that Clostridium spp. might play a role in this anaerobic biotransformation. These results expand our understanding of microbial metabolism of steroids under strictly anoxic conditions.